title: Participation of catalase in voluntary ethanol consumption in perinatally low-level lead-exposed rats.
abstract: BACKGROUND
  Environmental lead (Pb) exposure and alcohol abuse pose significant public health problems for our society. One of the proposed mechanisms of action of the developmental neurotoxicant Pb is related to its ability to affect antioxidant enzymes, including catalase (CAT). Ethanol's (EtOH) motivational effects are postulated to be mediated by the CAT-dependent acetaldehyde generated in the brain. The current study sought to investigate the role of this enzyme in the elevated EtOH intake previously reported in perinatally Pb-exposed rats.
  
  
  METHODS
  Thirty-five-day-old male Wistar rats exposed to 220 ppm Pb during gestation and lactation were offered escalating EtOH solutions (2 to 10%) or water, 2 h/d for 28 days. Once baseline 10% EtOH intake was achieved, they were injected with (i) saline (SAL), (ii) 3-amino 1,2,4 triazole (aminotriazole [AT], a CAT inhibitor, 250 mg/kg intraperitoneally [i.p.], 5 hours before the last 8 EtOH intake sessions), or (iii) 3-nitropropionic acid (3NPA; a CAT activator, 20 mg/kg subcutaneously [s.c.], 45 minutes before the last 4 EtOH intake sessions). Rats were then sacrificed, blood collected, and brain regions harvested for CAT activity determination. Additional studies evaluated EtOH intake and CAT activity in response to 10 and 30 mg/kg 3NPA. Both 3NPA and AT were evaluated for striatal cytotoxicity.
  
  
  RESULTS
  We observed that AT pretreatment blunted the increased EtOH intake, as well as the elevated CAT activity in blood, cerebellum, and hippocampus evidenced in the developmentally Pb-exposed rats that have consumed EtOH. Conversely, 20 mg/kg 3NPA further increased voluntary EtOH intake in these animals as compared with controls, concomitantly with a slight elevation in CAT activity both in blood and in the striatum, associated with no changes in striatal cytotoxicity.
  
  
  CONCLUSIONS
  These results suggest a participation of CAT, and possibly acetaldehyde, in Pb-induced high EtOH intake, and open up new avenues to elucidate the mechanism that underlies the Pb and EtOH interaction.
authors.affiliation: Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Córdoba, Argentina; Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Mara S
authors.initials: MS
authors.lastname: Mattalloni
authors.forename: Laura N
authors.initials: LN
authors.lastname: De Giovanni
authors.forename: Juan C
authors.initials: JC
authors.lastname: Molina
authors.forename: Liliana M
authors.initials: LM
authors.lastname: Cancela
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Virgolini
mesh_terms: D000428:Alcohol Drinking / Q000097:blood* / Q000188:drug therapy; D000640:Amitrole / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D015415:Biomarkers; D007854:Lead; D000431:Ethanol; D002374:Catalase; D000640:Amitrole
keywords: Acetaldehyde; Catalase; Ethanol Intake; Lead Exposure